Oxidation of disulfides with electrophilic halogenating reagents: concise methods for preparation of thiosulfonates and sulfonyl halides

The reaction of aromatic or benzylic disulfides with 2.5 equiv of Selectfluor™ in acetonitrile/water (10:1) at room temperature efficiently produced the corresponding thiosulfonates. Conversely, the reaction of disulfides with 6.5 equiv of Selectfluor™ or thiosulfonates with 4.5 equiv of Selectfluor™ in refluxing acetonitrile/water (10:1) provided sulfonyl fluorides in high yields. Accufluor™ and FP-T300™ are also effective in preparing sulfonyl fluorides from disulfides under the similar reaction conditions. Sulfonyl chlorides or sulfonyl bromides were effectively obtained from the reaction of disulfides with 6 equiv of either N-chlorosuccinimide or N-bromosuccinimide in acetonitrile/water (10:1) at room temperature. Some other electrophilic chlorinating or brominating reagents are also able to be used instead of N-chlorosuccinimide or N-bromosuccinimide for the syntheses of sulfonyl halides from disulfides. These reactions of disulfides with electrophilic halogenating reagents are convenient methods to prepare thiosulfonates and sulfonyl halides.     

Chemical ionization and electron impact mass spectra of thiosulfinates,thiosulfonates and sulfinyl sulfones

The chemical ionization and electron impact mass spectra of some thiosulfinates, thiosulfonates and sulfinyl sulfones have been studied. The electron impact mass spectra of four of the six thiosulfonates show molecular ions of less than 1%. Inconclusive evidence was obtained for sulfenyl sulfinate type intermediates in the electron impact spectra of thiosulfonates. The electron impact spectra of thiosulfonates were similar to those of thiosulfonates. The chemical ionization (isobutane) mass spectra of thiosulfinates and thiosulfonates generally show protonated molecular ions [MH]⁺ as base peaks and [MH+1]⁺ and [MH+2]⁺ peaks.     

Enantiospecific synthesis of substituted 1-norbornanesulfonic acids and 1-norbornanesulfenic and sulfonic acid derivatives

New homochiral 1-norbornanesulfenic and sulfonic acid derivatives 2–7, as well as the sulfonic acids 8, are easily synthesised starting from 2-methylene-1-norbornylthiotriflates 1. This new class of homochiral bridgehead thiosulfonates was prepared by us from naturally occurring (+)-camphor and (−)-fenchone. Nucleophilic substitution at the sulfenyl sulfur atom is the key step for this synthetic strategy.     

Ferrocenyl bis-phosphine ligands bearing sulfinyl,sulfonyl or sulfenyl groups: applications in asymmetric hydrogenation and allylic alkylation reactions

A new series of chiral ferrocenyl bis-phosphine ligands have been synthesized. Elements of planar and central chirality have been incorporated into a ferrocene backbone through sulfinyl, sulfonyl and sulfenyl groups at the ortho-position to the phosphines. The effectiveness of these ligands has been demonstrated in Rh-catalyzed hydrogenations and Pd-catalyzed allylic alkylations.     

Sulfonyl hydrazides as sulfonyl sources in organic synthesis

While sulfonyl hydrazides are widely utilized in organic synthesis, it is only in recent years that they have emerged as powerful sulfonyl sources. The hydrazinyl group can be readily removed from sulfonyl hydrazides under thermal, basic, oxidative, radical, and/or transition metal-catalyzed conditions, and subsequently, the remaining sulfonyl groups are able to form carbon-sulfur, sulfur-nitrogen, sulfur-halogen, sulfur-sulfur, and sulfur-selenium bonds with a wide variety of organic compounds, providing alternative approaches to the preparation of sulfones, sulfonamides, sulfonyl halides, thiosulfonates, and selenosulfonates. Moreover, some of the carbon-sulfur bond-forming reactions have been successfully applied to the construction of carbocycles, heterocycles, and stereogenic centers.     

Visible light induced decomposition of sulfonyl hydrazides using Pd/ZrO2 nanocomposite photocatalyst

A new approach to synthesis of thiosulfonates has been developed under mild conditions without any oxidants and promoting reagents through a Pd/ZrO₂ nanocomposite photocatalyst catalyzed decomposition of sulfonyl hydrazides. This protocol gave the products in moderate yields, comparable to the best results reported so far. Finally, a plausible reaction mechanism was proposed.     

Synthesis and Oxidative Transformations of New Chiral Pinane-Type γ-Ketothiols: Stereochemical Features of Reactions

Chiral γ-ketothiols, thioacetates, thiobenzoate, disulfides, sulfones, thiosulfonates, and sulfonic acids were obtained from β-pinene for the first time. New compounds open up prospects for the synthesis of other polyfunctional compounds combining a biologically active pinane fragment with various pharmacophore groups. It was shown that the syntheses of sulfanyl and sulfonyl derivatives based on 2-norpinanone are characterized by high stereoselectivity in comparison with similar reactions of pinocarvone. The conditions for the preparation of diastereomerically pure thioacetyl and thiobenzoyl derivatives based on pinocarvone, as well as for the chemoselective oxidation of γ-ketothiols with chlorine dioxide to the corresponding thiolsulfonates and sulfonic acids, were selected. The effect of the VO(acac)₂ catalyst on the increase in the yields of thiosulfonates was shown. A new direction of the transformation of thiosulfonates with the formation of sulfones was revealed. In the case of pinocarvone-based sulfones, the configuration is inversed at the C2 atom. An epimerization scheme is proposed.     

FeBr3-catalyzed regioselective hydroxysulfenylation of N-allylsulfonamides with sulfonyl hydrazides

Regioselective hydroxysulfenylation of unactivated CC double bonds was reported. Using FeBr₃-bpy as the catalyst, Na₂S₂O₈ as the oxidant, and sulfonyl hydrazides as the sulfenyl sources, hydroxysulfenylation of unfunctionalized olefins proceeded readily, giving a variety of β-hydroxysulfides in moderate to good isolated yields.     

Selective trapping of SNO-BSA and GSNO by benzenesulfinic acid sodium salt: mechanistic study of thiosulfonate formation and feasibility as a protein S-nitrosothiol detection strategy

The conversion of S-nitrosothiols to thiosulfonates by reaction with the sodium salt of benzenesulfinic acid (PhSO₂Na) has been examined in detail with the exemplary substrates S-nitrosoglutathione (GSNO) and S-nitrosylated bovine serum albumin (SNO-BSA). The reaction stoichiometry (2:1, PhSO₂Na:RSNO) and the rate law (first order in both PhSO₂Na and RSNO) have been determined under mild acidic conditions (pH 4.0). The products have been identified as the corresponding thiosulfonates (GSSO₂Ph and BSA-SSO₂Ph) along with PhSO₂NHOH obtained in a 1:1 ratio. GSH, GSSG, and BSA were unreactive to PhSO₂Na.     

Synthesis of New Thiosulfonates and Disulfides from Sulfonyl Chlorides and Thiols

Aromatic thiols were converted into thiosulfonates or disulfides, under very mild conditions, with fair to excellent yields, by using sulfonyl chloride as oxydant reagent.     

The mass spectral rearrangements of 1,6-bis(arylsulfenyl)-2,4-hexadiynes and 1,6-bis(arylsulfonyl)-2,4-hexadiynes

The mass spectral. behavior of 1,6-bis(arylsulfenyl)-2,4-hexadiynes and 1,6-bis(arylsulfonyl)-2,4-hexadiynes were examined. The sulfenyl derivatives extruded the hexadiynyl moiety with the formation of Ar? S? S? Ar fragments. The sulfonyl derivatives, on the other hand, showed no extrusion of the hexadiyne fragment but an expulsion of SO₂ and even two SO₂ units.     

Oxidation of disulfides with Selectfluor™: concise syntheses of thiosulfonates and sulfonyl fluorides

The reaction of aromatic or benzylic disulfides with 2.5 equiv of Selectfluor™ in acetonitrile/water (10:1) at room temperature efficiently produced the corresponding thiosulfonates. On the other hand, the reaction of disulfides with 6.5 equiv of Selectfluor™ in refluxing acetonitrile/water (10:1) provided sulfonyl fluoride in high yields.     

Pyridine and triphenylphosphine oxide activation of sulfonyl chlorides in the syntheses of (E) alk-1-enyl sulfones

This paper describes efficient and new approaches to (E) alk-1-enyl sulfones, starting from sulfonyl chloride/pyridine or sulfonyl chloride/triphenylphosphine complexes in the presence of (E) di-iso-butyl alk-1-enyl alanes.The use of CuCl in the presence of sulfonyl chloride/pyridine complexes or pyridine in the presence of sulfonyl chloride/triphenylphosphine complexes, respectively, results in a remarkable increase in the yields and conversions.     

Bi-functional fluoroalkylation reagents: an introduction to halo-substituted 3-oxa-perfluoroalkanesulfonyl fluorides

X(CF₂CF₂)_nOCF₂CF₂SO₂F (X=I, Br, Cl; n=1, 2, 3, 4) are widely used fluoroalkylation reagents, which can incorporate ‘heavy’ fluorous tags into organic compounds. X(CF₂CF₂)_nOCF₂CF₂SO₂F have both sulfonyl and halo groups. They behave as bi-functional fluoroalkylation reagents. The cleavage of the C–I bonds of I(CF₂CF₂)_nOCF₂CF₂SO₂F by reductants (such as Na₂S₂O₄, Zn), single electron transfer reagents and radical initiator systems (like Bz₂O₂, AIBN, and (t-BuO)₂, or under UV and heat) gives, respectively, the sulfinatodehalogenated products, the hydrodehalogenated products, the homo-coupling products and the perfluoroalkylated products (if alkenes, alkynes or arenes were added). The functionalization of the sulfonyl groups (SO₂F) of X(CF₂CF₂)_nOCF₂CF₂SO₂F by esterification, amidation, and fluorination affords the corresponding perfluoroalkanesulfonates, fluoroalkanesulfonamide, and perfluoroalkanes. In many cases, both the halo and sulfonyl groups of X(CF₂CF₂)_nOCF₂CF₂SO₂F are transformed. These transformations finally lead to hundreds of useful highly fluorinated materials, such as supper acids, catalysts, surfactants, ion-exchange resins, electrolytes, polymers, and dense ionic liquids. Furthermore, X(CF₂CF₂)_nOCF₂CF₂SO₂F have commendable advantages, such as the easy preparation, the wide range of substrate tolerance, the mild reaction condition, and the high yields of desired products, which make them very promising. This review briefly summarizes the synthesis, reactivity, and applications of these intriguing reagents.     

Enantiomeric purity enrichment of (R)-tetrahydrothiophene-3-ol sulfonyl derivatives by crystallization

(R)-Tetrahydrothiophene-3-ol sulfonyl derivatives 3–19 were prepared by introduction of various sulfonyl groups at the hydroxyl group of (R)-tetrahydrothiophene-3-ol 1 with low enantiomeric purity (68–74% ee). Crystallization was applied to improve their enantiomeric purity. Improvement in enantiomeric purity depended on the introduced sulfonyl group. The enantiomeric purity of enantiomeric sulfonyl derivatives was improved to more than 90% ee by simple crystallization without using seed crystals. These products from crystallization provided not only higher %ee crystals but also a higher %ee mother liquor. The enantiomeric purity of diastereomeric sulfonyl derivatives was improved remarkably, and the product of the derivative 18 provided the mother liquor with 100% de. Crystallization of these sulfonyl derivatives showed a novel and interesting feature that mother liquors with high enantiomeric purity were obtained in many cases.     

Simultaneous Determination of Cimetidine and Related Compounds in Pharmaceuticals by HPLC on a Porous Graphitic Carbon Column

A high-performance liquid chromatographic method has been developed for determination of cimetidine and its main related compounds, 4-hydroxymethyl-5-methylimidazol (MH), N-cyano-N',N''-dimethylguanidine (Carbonate), 1-methyl-3-[2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfonyl]ethyl]guanidine (Guanidine), 2-cyano-1-methyl-3-[2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfonyl] (Sulfoxide), and 1-[(methylamino)[[2-[[(5-methyl-1H-imidazol-4-yl)methyl]sulfonyl]ethyl]amino]methylene]urea (Amide). Chromatographic separation was achieved on a porous graphitic carbon (PGC) column with a gradient 17:83 to 19:81 (v/v) acetonitrile-0.05 M potassium phosphate buffer containing 0.40% pentane sulfonic acid at pH 2.5. Analysis was performed at a flow-rate of 1 mL min^?1 and the detection wavelength was 228 nm. Calibration plots were linear in the concentration ranges 0.25 to 83 µg mL^?1 for cimetidine and Carbonate, 0.25 to 75 µg mL^?1 for Guanidine, Amide, and Sulfoxide, and 0.25 to 100 µg mL^?1 for MH, with correlation coefficients (R ²) between 0.9990 and 0.9998. The lowest detectable concentration of cimetidine and Amide was 0.07 µg mL^?1; for MH, Carbonate, Guanidine, and Sulfoxide it was 0.06 µg mL^?1. Method repeatability (intraday) and reproducibility (interday) was always less than 2% (n=5). The proposed liquid chromatographic method was successfully used for analysis of commercially available cimetidine dosage forms; recoveries were from 99.2 to 100.8%.     

Strong dual-state emission of unsymmetrical and symmetrical thiazolothiazole-bridged imidazolium salts

A novel thiazolothiazole-bridged imidazole derivative (1) was found to exhibit blue fluorescence in gaseous state or in methanol and yellow fluorescence in solid state. The N-alkylation of imidazole subunit(s) in 1 using n-propyl iodide generated unsymmetrically or symmetrically alkylated thiazolothiazole-bridged imidazolium salts with good water solubility and remarkably strong emission in solution. Furthermore, the replacement of iodide counter-anion by triflate or bis(trifluoromethane sulfonyl)imide achieved remarkably strong emission in solid state and in solution as well as good water solubility. The strong fluorescence of dicationic salts with triflate and NTf₂^– counter-anions in solid state can be ascribed to their twisted and rigid structures induced by interionic C?H···F hydrogen bonding.     

Unexpected conversions of selected heteroorganic compounds

A few unexpected conversions of selected heteroorganic compounds are described, including the formation of N‐sulfonyl sulfenamide derivatives and the mixed phosphinyl‐sulfenyl anhydrides in the reactions of sulfinyl chlorides with α‐phenylethylamine or t‐butyl‐phenylphosphine oxide, respectively. Unexpected reactions of the ortho hydroxyalkyl‐substituted diaryl sulfoxides and hypervalent sulfur and selenium derivatives, induced by triphenylphosphine, are also presented. Attempts to rationalize the observed reaction courses are briefly discussed. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:437–442, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10077     

Introduction of N,N'-disulfonylhydrazines as new sulfonylating reagents for highly efficient synthesis of (E)-β-iodovinyl arenesulfones under mild conditions

N,N'-Disulfonylhydrazines have been proven to be the most reactive precursors of the sulfonyl radicals among all types of sulfonyl substituted hydrazines as early as half a century ago. However, the sulfonyl radicals generated from these compounds have not been used in organic synthesis except the simple self-dimerization synthesis of disulfones controlled by the “solvent-cage-effects”. In this article, N,N′-disulfonylhydrazines were introduced as new sulfonylating reagents and their combinations with NIS were disclosed as new iodosulfonylating reagents of alkynes. Finally, a highly efficient method for the synthesis of (E)-β-iodovinyl arenesulfones was developed by mixing an alkyne, a N,N′-disulfonyl-hydrazine and NIS in aqueous THF at room temperature for 5 min.     

Formation of an unexpected rearrangement product using Grubbs’ second generation catalyst: 2-allyl-3,4-dihydro-2H-1,4-benzothiazines from diene precursors

Application of sub-stoichiometric amounts of Grubbs’ second generation catalyst to the substrate N-allyl-N-[2-(allylsulfanyl)phenyl]-4-methylbenzenesulfonamide afforded the ring-closed compound 6-[(4-methylphenyl)sulfonyl]-5,6-dihydro-2H-1,6-benzothiazocine, as well as the unexpected 2-allyl-4-[(4-methylphenyl)sulfonyl]-3,4-dihydro-2H-1,4-benzothiazine. Use of similar conditions on an analogous sulfoxide resulted in the expected product, 6-[(4-methylphenyl)sulfonyl]-5,6-dihydro-2H-1,6-benzothiazocine 1-oxide, indicating that the sulfide was playing a key role in this novel transformation. Furthermore, the use of N-allyl-4-methyl-N-{2-[(2-methyl-2-propenyl)sulfanyl]phenyl}-benzenesulfonamide in the same reaction gave 2-(2-methyl-2-propenyl)-3,4-dihydro-2H-1,4-benzothiazine.